By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

Objective To investigate the relationship between the levels of Versican(VCAN)and Cyclin D1(CCND1)in peripheral blood and the progression and prognosis of multiple myeloma(MM).Methods A total of 121 patients with MM(MM group)and 109 healthy volunteers(control group)were selected and admitted to the Department of Hematology of Suzhou Municipal Hospital from January 2018 to May 2022.According to the International Staging System(ISS),the patients with MM were divided into a stage I group(n=46),a stage II group(n=41),and a stage III group(n=34).Real time fluorescence quantitative PCR(RT-PCR)was used to detect the expression levels of VCAN mRNA and CCND1 mRNA in peripheral blood,the patients were followed up for 24 months after discharge to make statistics on the survival of MM patients.The VCAN mRNA and CCND1 mRNA expression in the peripheral blood of MM patients with different ISS was compared.Kaplan-Meier method was used to draw the survival curve of MM,and multi-factor COX proportional regression analysis was established to analyze the factors affecting the prognosis of MM patients.Results The expressions of VCAN mRNA(2.69±0.63)and CCND1 mRNA(3.29±0.63)in peripheral blood of MM group were higher than those of control group(1.32±0.46,1.53±0.37),and the differences were statistically significant(t=18.659,25.473,all P<0.05).The expressions of VCAN mRNA(3.05±0.31)and CCND1 mRNA(3.75±0.21)in peripheral blood of stage Ⅲ group were higher than those of stage Ⅱ(2.76±0.31,3.29±0.36)and stage Ⅰ groups(2.36±0.25,2.95±0.29),and the differences were statistically significant(t=7.626～16.831,all P<0.05).During the follow-up period,1 case was lost to follow-up,36 cases died and 84 cases survived.The overall survival rate of patients with high VCAN mRNA(58.06%)and CCND1 mRNA(57.14%)expression MM was lower than that of patients with low VCAN mRNA(82.76%)and CCND1 mRNA(84.21%),and the differences were statistically significant(χ2=8.727,10.820,all P<0.05).The age of the death group was higher than that of the survival group(t=3.020),ISS stage III,and bone marrow cells proportion≥60%,chromosome karyotype 1q21+proportion,peripheral blood VCAN mRNA and CCND1 mRNA i expression were all higher than those of the survival group(t/χ2=5.988～8.589),and the differences were statistically significant(all P<0.05),respectively.Multivariate COX risk ratio analysis,ISS stage III,high expression of VCAN mRNA and CCND1 mRNA were risk factors for death in MM patients during follow-up(Wald χ2=10.672,5.682,5.969,all P<0.05).Conclusion The expression of VCAN mRNA and CCND1 mRNA in peripheral blood of MM patients is significantly increased,which is related to high clinical stage and poor prognosis.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Various growth factors are key molecules in wound healing and exert regulatory effects at all stages of healing. Fibroblast growth factors (FGFs), with their prominent pro-growth activity, play a crucial role in promoting proliferation during the proliferative phase of wound healing. By binding to fibroblast growth factor receptors, FGFs activate downstream signaling pathways to regulate wound inflammation, reduce oxidative stress, promote cell proliferation, angiogenesis, and extracellular matrix remodeling. This facilitates the transition of wounds from the " inflammatory phase" to the " proliferative phase" and enhances proliferative healing. The clinical therapeutic value of FGFs in acute and chronic wounds has been widely confirmed, but their full efficacy is limited by issues such as short half-life and poor delivery efficiency. Research focusing on innovative FGF delivery materials and molecular modification strategies will become a key direction to break through current therapeutic bottlenecks and unlock their greater therapeutic potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.

Objective To investigate the relationship between the levels of Versican(VCAN)and Cyclin D1(CCND1)in peripheral blood and the progression and prognosis of multiple myeloma(MM).Methods A total of 121 patients with MM(MM group)and 109 healthy volunteers(control group)were selected and admitted to the Department of Hematology of Suzhou Municipal Hospital from January 2018 to May 2022.According to the International Staging System(ISS),the patients with MM were divided into a stage I group(n=46),a stage II group(n=41),and a stage III group(n=34).Real time fluorescence quantitative PCR(RT-PCR)was used to detect the expression levels of VCAN mRNA and CCND1 mRNA in peripheral blood,the patients were followed up for 24 months after discharge to make statistics on the survival of MM patients.The VCAN mRNA and CCND1 mRNA expression in the peripheral blood of MM patients with different ISS was compared.Kaplan-Meier method was used to draw the survival curve of MM,and multi-factor COX proportional regression analysis was established to analyze the factors affecting the prognosis of MM patients.Results The expressions of VCAN mRNA(2.69±0.63)and CCND1 mRNA(3.29±0.63)in peripheral blood of MM group were higher than those of control group(1.32±0.46,1.53±0.37),and the differences were statistically significant(t=18.659,25.473,all P<0.05).The expressions of VCAN mRNA(3.05±0.31)and CCND1 mRNA(3.75±0.21)in peripheral blood of stage Ⅲ group were higher than those of stage Ⅱ(2.76±0.31,3.29±0.36)and stage Ⅰ groups(2.36±0.25,2.95±0.29),and the differences were statistically significant(t=7.626～16.831,all P<0.05).During the follow-up period,1 case was lost to follow-up,36 cases died and 84 cases survived.The overall survival rate of patients with high VCAN mRNA(58.06%)and CCND1 mRNA(57.14%)expression MM was lower than that of patients with low VCAN mRNA(82.76%)and CCND1 mRNA(84.21%),and the differences were statistically significant(χ2=8.727,10.820,all P<0.05).The age of the death group was higher than that of the survival group(t=3.020),ISS stage III,and bone marrow cells proportion≥60%,chromosome karyotype 1q21+proportion,peripheral blood VCAN mRNA and CCND1 mRNA i expression were all higher than those of the survival group(t/χ2=5.988～8.589),and the differences were statistically significant(all P<0.05),respectively.Multivariate COX risk ratio analysis,ISS stage III,high expression of VCAN mRNA and CCND1 mRNA were risk factors for death in MM patients during follow-up(Wald χ2=10.672,5.682,5.969,all P<0.05).Conclusion The expression of VCAN mRNA and CCND1 mRNA in peripheral blood of MM patients is significantly increased,which is related to high clinical stage and poor prognosis.

Various growth factors are key molecules in wound healing and exert regulatory effects at all stages of healing. Fibroblast growth factors (FGFs), with their prominent pro-growth activity, play a crucial role in promoting proliferation during the proliferative phase of wound healing. By binding to fibroblast growth factor receptors, FGFs activate downstream signaling pathways to regulate wound inflammation, reduce oxidative stress, promote cell proliferation, angiogenesis, and extracellular matrix remodeling. This facilitates the transition of wounds from the " inflammatory phase" to the " proliferative phase" and enhances proliferative healing. The clinical therapeutic value of FGFs in acute and chronic wounds has been widely confirmed, but their full efficacy is limited by issues such as short half-life and poor delivery efficiency. Research focusing on innovative FGF delivery materials and molecular modification strategies will become a key direction to break through current therapeutic bottlenecks and unlock their greater therapeutic potential.

With the rapid development of preimplantation genetic testing (PGT) technology in recent years, risks in clinical application have arisen at the same time. Related risks include identification of pathogenic variants for PGT, negative impact of disease for PGT on ovarian reservation in female carriers, control of ovarian stimulation, and safety of ovarian simulation in hereditary cancer gene carriers. Risk management should be performed in different steps of the PGT processes.

With the rapid development of preimplantation genetic testing (PGT) technology in recent years, risks in clinical application have arisen at the same time. Related risks include identification of pathogenic variants for PGT, negative impact of disease for PGT on ovarian reservation in female carriers, control of ovarian stimulation, and safety of ovarian simulation in hereditary cancer gene carriers. Risk management should be performed in different steps of the PGT processes.